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hnRNP K Coordinates Transcriptional Silencing by SETDB1 in Embryonic Stem Cells


Retroelements, including endogenous retroviruses (ERVs), pose a significant threat to genome stability. In mouse embryonic stem (ES) cells, the enzyme SETDB1 safeguards the genome against transcription of specific ERVs by depositing a repressive mark H3K9 trimethylation (H3K9me3). Although SETDB1 is recruited to ERVs by its binding partner KAP1, the molecular basis of this silencing pathway is not clear. Using biochemical and genetic approaches, we identified hnRNP K as a novel component of this silencing pathway that facilitates the recruitment of SETDB1 to ERVs to promote their repression. HnRNP K binds to ERV sequences via KAP1 and subsequently promotes SETDB1 binding. Together, our results reveal a novel function for hnRNP K in transcriptional silencing of ERVs and demonstrate a new regulatory mechanism governing the deposition of H3K9me3 by SETDB1 in ES cells.


Vyšlo v časopise: hnRNP K Coordinates Transcriptional Silencing by SETDB1 in Embryonic Stem Cells. PLoS Genet 11(1): e32767. doi:10.1371/journal.pgen.1004933
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004933

Souhrn

Retroelements, including endogenous retroviruses (ERVs), pose a significant threat to genome stability. In mouse embryonic stem (ES) cells, the enzyme SETDB1 safeguards the genome against transcription of specific ERVs by depositing a repressive mark H3K9 trimethylation (H3K9me3). Although SETDB1 is recruited to ERVs by its binding partner KAP1, the molecular basis of this silencing pathway is not clear. Using biochemical and genetic approaches, we identified hnRNP K as a novel component of this silencing pathway that facilitates the recruitment of SETDB1 to ERVs to promote their repression. HnRNP K binds to ERV sequences via KAP1 and subsequently promotes SETDB1 binding. Together, our results reveal a novel function for hnRNP K in transcriptional silencing of ERVs and demonstrate a new regulatory mechanism governing the deposition of H3K9me3 by SETDB1 in ES cells.


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